The human heart wall consists of an inner layer of simple squamous epithelium, referred to as the endocardium, overlying a variably thick heart muscle or myocardium and is enveloped within a multi-layer tissue structure referred to as the pericardium. The innermost layer of the pericardium, referred to as the visceral pericardium or epicardium, clothes the myocardium. The epicardium reflects outward at the origin of the aortic arch to form an outer tissue layer, referred to as the parietal pericardium, which is spaced from and forms an enclosed sac extending around the visceral pericardium of the ventricles and atria. An outermost layer of the pericardium, referred to as the fibrous pericardium, attaches the parietal pericardium to the sternum, the great vessels and the diaphragm so that the heart is confined within the middle mediastinum. Normally, the visceral pericardium and parietal pericardium lie in close contact with each other and are separated only by a thin layer of a serous pericardial fluid that enables friction free movement of the heart within the sac. The space (really more of a potential space) between the visceral and parietal pericardia is referred to as the pericardial space. In common parlance, the visceral pericardium is usually referred to as the epicardium, and epicardium will be used hereafter. Similarly, the parietal pericardium is usually referred to as the pericardium, and pericardium will be used hereafter in reference to parietal pericardium.
Access to the pericardial space is desirable in order to provide a variety of cardiac therapies, including delivery of therapeutic agents (defined herein as including genetic agents, biologic agents, and pharmacologic agents), placement of electrical medical leads for pacing, cardioversion, defibrillation or EGM monitoring, removal of pericardial fluid for diagnostic analysis, or other purposes. A variety of mechanisms have been developed for accessing the pericardial space, ranging from a simple puncture by means of a large bore needle to intricate catheter or cannula based systems provided with sealing and anchoring mechanisms.
Access to the pericardial space may be accomplished from outside the body by making a thoracic or sub-xiphoid incision to access and cut or pierce the pericardial sac. Access to the pericardial space from the exterior of the body, accomplished by passing a cannula or catheter type device through the chest wall and thereafter passing the cannula or catheter or a further instrument through the pericardium into the pericardial space, is disclosed in U.S. Pat. Nos. 5,827,216, 5,900,433, and 6,162,195 issued to Igo, U.S. Pat. No. 5,336,252 issued to Cohen, and U.S. Pat. Nos. 5,972,013, 6,206,004, 6,592,552 by Schmidt, for example. In certain cases the pericardial sac is cut by a cutting instrument as disclosed in U.S. Pat. Nos. 5,931,810, 6,156,009, and 6,231,518 issued to Grabek et al.
Alternatively, an elongated perforating instrument device is introduced from a skin incision by a transvenous or transarterial approach into the right or left heart chambers, respectively, and a cutting or piercing or penetrating mechanism at the distal end of the elongated perforating instrument is operated to penetrate through the atrial or ventricular wall of the right or left heart chamber into the surrounding pericardial space without perforating the pericardial sac. For example, a transvenous catheter provided with a hollow helical needle adapted to rotated and pierce through the wall of a right or left heart chamber to access the pericardial space to deliver pharmacologic agents is disclosed in U.S. Pat. No. 5,797,870 issued to March et al. A transvenous catheter introduced into the right ventricular chamber to provide access through the right ventricular wall to enable passage of an electrical medical lead into the pericardial space is disclosed in, U.S. Pat. No. 4,991,578 issued to Cohen, and U.S. Pat. No. 5,330,496 issued to Alferness, for example.
It is preferable to effect transvenous access into the pericardial space from the right atrial heart chamber through the atrial wall due to the relatively low blood pressure of right atrial blood during systole to lessen the possibility of leakage of blood into the pericardial space. Consequently, it has been proposed to transvenously introduce an elongated electrical medical device through the venous system and either the inferior vena cava or the superior vena cava into the right atrial chamber and perforating through the right atrial wall into the pericardial space. In U.S. Pat. No. 4,946,457 issued to Elliot it is proposed to transvenously introduce an elongated electrical medical lead through the venous system and superior vena cava into the right atrial chamber and perforating through the right atrial wall to advance and dispose the distal electrode of the lead into the pericardial space. It has also been proposed that a preferred site of penetration of catheters or electrical medical leads through the atrial wall into the pericardial space is within the right atrial appendage as disclosed in U.S. Pat. No. 5,269,326 issued to Verrier, U.S. Pat. No. 6,200,303 issued to verrier et al and U.S. Pat. No. 5,968,010 issued to Waxman et al. Transvenous approaches through either of the inferior vena cava or the superior vena cava are disclosed in these patents.
It is customary in the implantation of transvenous cardiac pacing leads and cardioversion/defibrillation leads to access the venous system that drains into the superior vena cava and to lodge and fix a pace/sense or cardioversion/defibrillation electrode within the right ventricle, the right atrium or a cardiac vein accessed through the coronary sinus. The proximal connector ends of such leads are coupled to implantable pulse generators (IPGs) that are implanted subcutaneously in the thoracic region. It is preferable to implant the IPGs in the thoracic region, rather than the groin or abdominal region, because the thoracic region is more stable than the abdominal or groin region during ambulation and other normal body movement and the IPG is less likely to migrate from the subcutaneous implantation site. Consequently, the transvenous access into the right atrium is made through the superior vena cava.
A distal pace/sense electrode of an atrial pacing lead is typically lodged into the atrial appendage and various active and passive fixation mechanisms are employed to hold the electrode in place. Atrial pacing leads have been designed in a variety of ways to overcome the inherent difficulty of routing the distal end of an atrial lead or any other elongated medical device through the superior vena cava into the right atrial heart chamber and then into the atrial appendage. However, care is taken in the design of such leads and delivery mechanisms and techniques to avoid perforating the atrial wall.
It is proposed in the above-referenced '326 patent to alternatively route a pacing lead or cardioversion/defibrillation lead through a perforation of the atrial wall in the atrial appendage to lodge a pace/sense electrode and/or cardioversion/defibrillation electrode within the pericardial space and to subcutaneously implant an IPG or implantable monitor or drug dispenser in the thoracic region. The suggested routing of the electrical medical lead or catheter is through the thoracic venous system, through the superior vena cava, and through the atrial wall of the atrial appendage into the pericardial space.
It is a relatively simple matter to route a perforating instrument through the venous system draining into the right atrium through the inferior vena cava since the instrument body is relatively straight within the right atrium and axial force can be applied to perforate the atrial wall while observing the advancement under fluoroscopy. It is not a simple matter to advance the distal end perforating mechanisms of the perforating instruments disclosed in the above-identified patents through the superior vena cava into the right atrial heart chamber and then into the atrial appendage. The physiology and shape of the atrial appendage requires that the direction of advancement of the distal end be reversed or abruptly changed after it is disposed in the right atrial heart chamber. Moreover, the atrial wall in the atrial appendage tends to yield somewhat if blunt force is applied against its endocardial surface. Consequently, the precise application of perforating force and advancement of the distal end perforating element must be carefully controlled, which is difficult to manage through the bend in the instrument body.
It would therefore be desirable to provide a method and system for accessing the atrial appendage via the superior vena cava and applying force through an elongated perforating instrument sufficient to safely penetrate through or perforate the atrial wall without penetrating or perforating the pericardial sac enclosing the pericardial space.
In addition, after the perforation is made, the transvenous advancement of an electrical medical lead or therapeutic catheter through the perforation made in the atrial wall via the superior vena cava can be difficult to accomplish. It would be desirable that such a system and method facilitate that advancement.
It would also be particularly desirable to facilitate access to the pericardial space to enable chronic delivery of pharmacologic agents to the heart as suggested in the above-referenced '326, '303, and '010 patents. In particular it is noted that the pericardial fluid provides an excellent medium for delivery of pharmacologic agents to the cardiac muscles and coronary vessels without distribution to other organs. Among the clinically significant pharmacologic agents (i.e., drugs) which could advantageously be delivered to the heart via the pericardial fluid are those which improve cardiac contractility (e.g., digitalis drugs, adrenergic agonists, etc.), suppress arrhythmias (e.g., class I, II, III, and IV agents and specialized drugs such as amiodarone, which is particularly potent but has severe systemic side effects), dilate coronary arteries (e.g., nitroglycerin, calcium channel blockers, etc.), and lyse clots in the coronary circulation (e.g., thrombolytic agents such as streptokinase or tissue-type plasminogen activator (TPA)).
Examples of other pharmacologic agents which may be administered into the pericardial space include: agents to protect the heart pharmacologically from the toxic effects of drugs administered to the body generally for other diseases, such as cancer; antibiotics, steroidal and non-steroidal medications for the treatment of certain pericardial diseases; and growth factors to promote angiogenesis or neovascularization of the heart.
The delivery of further pharmacologic agents into the pericardial space is disclosed in the above-referenced '433 patent, wherein cardio-active or cardio-vascular active drugs are selected from vasodilator, antiplatelet, anticoagulant, thrombolytic, anti-inflammatory, antiarrhythmic, inotropic, antimitotic, angiogenic, antiatherogenic and gene therapy bioactive agents. The approaches to the pericardial space include those disclosed in the above-referenced '326 patent or transthoracically, e.g., under the xiphoid process, i.e., by a sub-xiphoid surgical approach.
In particular, it is proposed in the '433 patent to deliver such pharmacologic agents into the pericardial space to treat or to prevent vascular thrombosis and angioplasty restenosis, particularly coronary vascular thrombosis and angioplasty restenosis, thereby to decrease incidence of vessel rethrombosis, unstable angina, myocardial infarction and sudden death. It is proposed to deliver a congener of an endothelium-derived bioactive agent, more particularly a nitrovasodilator, representatively the nitric oxide donor agent sodium nitroprusside, to the pericardial space at a therapeutically effective dosage rate to abolish cyclic coronary flow reductions (CFR's) while reducing or avoiding systemic effects such as suppression of platelet function and bleeding. Particular congeners of an endothelium-derived bioactive agent include prostacyclin, prostaglandin E1, and a nitrovasodilator agent. Nitrovasodilater agents include nitric oxide (NOX) and NOX donor agents, including L-arginine, sodium nitroprusside and nitroglycycerine. The so-administered nitrovasodilators are effective to provide one or more of the therapeutic effects of promotion of vasodilation, inhibition of vessel spasm, inhibition of platelet aggregation, inhibition of vessel thrombosis, and inhibition of platelet growth factor release, at the treatment site, without inducing systemic hypotension or anticoagulation.
The above-referenced '433 patent also discloses intrapericardial injection of drugs for the treatment of malignant or loculated pericardial effusions in man. Drugs that have been injected into the pericardial space include antibiotic, antineoplastic, radioactive and fibrinolytic agents. This method of site-specific drug delivery has been shown to be effective in attaining higher, longer-lasting drug levels in the pericardial fluid with lower plasma concentrations and less systemic toxicity.
It is therefore desirable to provide a system and method for chronically accessing the pericardial space to deliver such therapeutic agents to treat cardiac disorders or to prevent or ameliorate a cardiac insult.